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X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome(MRXS32)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: MRXS32
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
Concept ID:
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
Gene (location): CLIC2 (Xq28)
Monarch Initiative: MONDO:0010473
OMIM®: 300886
Orphanet: ORPHA324410


X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome is a rare X-linked syndromic intellectual disability disorder characterized by profound intellectual disability, global developmental delay with absent speech, seizures, large joint contractures, abnormal position of thumbs and middle-age onset of cardiomegaly and atrioventricular valve abnormalities, resulting in subsequent congestive heart failure. Additional features include variable facial dysmorphism (notably large ears with overfolded helix) and large testes. [from ORDO]

Clinical features

From HPO
MedGen UID:
Concept ID:
The presence of abnormally large testes.
MedGen UID:
Concept ID:
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Congestive heart failure
MedGen UID:
Concept ID:
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
MedGen UID:
Concept ID:
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
MedGen UID:
Concept ID:
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
MedGen UID:
Concept ID:
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Spastic tetraplegia
MedGen UID:
Concept ID:
Disease or Syndrome
Spastic paralysis affecting all four limbs.
Global developmental delay
MedGen UID:
Concept ID:
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Absent speech
MedGen UID:
Concept ID:
Complete lack of development of speech and language abilities.
Intellectual disability, profound
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
MedGen UID:
Concept ID:
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
MedGen UID:
Concept ID:
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked intellectual disability-cardiomegaly-congestive heart failure syndrome
Follow this link to review classifications for X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome in Orphanet.

Recent clinical studies


Shalata A, Bar-Shai M, Hadid Y, Mahroum M, Mintz H, Shalata ZE, Radzishevsky E, Genizi J, Lorber A, Ben-Yosef T, Yaniv L
Genes (Basel) 2023 Jul 27;14(8) doi: 10.3390/genes14081539. PMID: 37628591Free PMC Article
Kumps C, D'haenens E, Vergult S, Leus J, van Coster R, Jansen A, Devriendt K, Oostra A, Vanakker OM
Clin Genet 2021 Mar;99(3):449-456. Epub 2021 Jan 5 doi: 10.1111/cge.13901. PMID: 33340101
Afrin A, Prokop JW, Underwood A, Uhl KL, VanSickle EA, Baruwal R, Wajda M, Rajasekaran S, Bupp C
Cold Spring Harb Mol Case Stud 2020 Dec;6(6) Epub 2020 Dec 17 doi: 10.1101/mcs.a005868. PMID: 33335012Free PMC Article


Kumps C, D'haenens E, Vergult S, Leus J, van Coster R, Jansen A, Devriendt K, Oostra A, Vanakker OM
Clin Genet 2021 Mar;99(3):449-456. Epub 2021 Jan 5 doi: 10.1111/cge.13901. PMID: 33340101

Clinical prediction guides

Piché J, Van Vliet PP, Pucéat M, Andelfinger G
Cell Cycle 2019 Nov;18(21):2828-2848. Epub 2019 Sep 13 doi: 10.1080/15384101.2019.1658476. PMID: 31516082Free PMC Article
Yardeni M, Weisman O, Mandel H, Weinberger R, Quarta G, Salazar-Mendiguchía J, Garcia-Pavia P, Lobato-Rodríguez MJ, Simon LF, Dov F, Arad M, Gothelf D
Am J Med Genet A 2017 Sep;173(9):2461-2466. Epub 2017 Jun 19 doi: 10.1002/ajmg.a.38320. PMID: 28627787Free PMC Article

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